Inhibition of Bacterial Esterases by Chloramphenicol (Chloromycetin)

Abstract

Recently a series of experiments have been undertaken to determine the interrelationships between bacterial enzymes and the new antibiotic chloramphenicol. It was hoped that some inhibitory action of this drug on a given enzymatic system could be detected which might help to explain the mode of action of the compound on bacterial celLs. At the present time the inhibitory action of chloramphenicol has been tested on approximately 45 isolated enzymatic systems. The results obtained in our laboratory from these experiments have demonstrated that the antibiotic does not inhibit cellular respiration of either resting or actively growing bacterial cells. The utilization of carbohydrates with the production of organic acids by way of the phosphorylation cycle was also not blocked (Smith and Worrel, unpublished). Furthermore, the breakdown of proteins into amino acids and their tranmination were not influenced (Smith and Worrel, in press). These studies and related observations on the inhibitory action of chloramphenicol on phosphatases, nucleases, and oxidizing enzymes suggested the possibility that chloramphenicol might be inhibiting the metabolism of fats and related organic acid esters. Two possible types of reactions would be involved in this general metabolic process, namely, the hydrolysis of the fat or ester and the utilization of the resulting organic acid and alcohol. The present paper deals with a few of the observations made on the inhibitory action of chloramphenicol on bacterial esterases that are involved in the hydrolysis and synthesis of fatty acid esters.

SOME ENZYMATIC ACTIVITIES OF A PARTICULATE FRACTION FROM SONIC LYSATES OF ESCHERICHIA COLI

“…NaF (0.06 M) was used to inhibit any ATPase present; 20 /Amoles of adenosine diphosphate was used as the acceptor for high energy phosphate. Lipase activity was measured by a method (Smith et al, 1949) in which tributyrin and triolein were used as substrates. Catalase activity was determined manometrically.…”

Observations on Mycobacterial Esterases With a Series of Synthetic Substrates

“…Experiments with monobutyrin and tributyrin as substrates were conducted manometrically (Smith et al, 1949). The volume of CO liberated was recorded at 10 minute intervals for a total of 30 minutes beginning 5 minutes after tipping in the substrate.…”

Symposium on the Mode of Action of Antibiotics1

“…Additional evidence supporting this possible mode of action will be given in a later part of this discussion. (Smith et al,82).…”

“…Here again the same responses were obtained as was found with the bacterial esterase. This The influence of chloromycetin on the esterase activity of mitochondria (Smith et al, 82).…”